PMID- 31780358 OWN - NLM STAT- MEDLINE DCOM- 20211029 LR - 20211029 IS - 1995-9133 (Electronic) IS - 1684-1182 (Linking) VI - 54 IP - 3 DP - 2021 Jun TI - Anti-IFN-gamma therapy alleviates acute lung injury induced by severe influenza A (H1N1) pdm09 infection in mice. PG - 396-403 LID - S1684-1182(18)30438-9 [pii] LID - 10.1016/j.jmii.2019.07.009 [doi] AB - BACKGROUND/PURPOSE: Severe infection with influenza A (H1N1)pdm09 virus is characterized by acute lung injury. The limited efficacy of anti-viral drugs indicates an urgent need for additional therapies. We have previously reported that neutralization of gamma interferon (IFN-gamma) could significantly rescue the thymic atrophy induced by severe influenza A (H1N1)pdm09 infection in BALB/c mice. A deeper investigation was conducted into the influence of neutralizing IFN-gamma to the BALB/c mice weight, survival rate, and lung injury. METHODS: The BALB/c mice was infected with severe influenza A (H1N1)pdm09. Monoclonal antibodies against IFN-gamma were injected into the abdominal cavities of the mice. After neutralization of IFN-gamma occurred in mice infected by severe \ influenza A (H1N1)pdm09, observing the influence of neutralizing IFN-gamma to the BALB/c mice weight, survival rate, lung injury. RESULT: Our results here showed that anti-IFN-gamma therapy alleviated the acute lung injury in this mouse model. Neutralization of IFN-gamma led to a significant reduction in the lung microvascular leak and the cellular infiltrate in the lung tissue, and also improved the outcome in mice mortality. Several pro-inflammatory cytokines, including interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha and granulocyte-colony stimulating factor (G-CSF) in the bronchoalveolar lavage fluid (BALF), and the chemokines including G-CSF, monocyte chemoattractant protein-1 (MCP-1) in serum samples were found to be significantly reduced after anti-IFN-gamma treatment. CONCLUSION: These results suggested that IFN-gamma plays an important role in acute lung injury induced by severe influenza A (H1N1)pdm09 infection, and monoclonal antibodies against IFN-gamma could be useful as a potential therapeutic remedy for future influenza pandemics. CI - Copyright (c) 2019. Published by Elsevier B.V. FAU - Liu, Bo AU - Liu B AD - Department of Pulmonary and Critical Care Medicine, Linzi District People's Hospital, Huangong Road, Zibo City, Shandong Province, China; Department of Clinical Microbiology, Linzi District People's Hospital, Huangong Road, Zibo City, Shandong Province, China; Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Huangong Road, Zibo City, Shandong Province, China; Linzi District People's Hospital Affiliated to Binzhou Medical University, Huangong Road, Zibo City, Shandong Province, China. FAU - Bao, LinLin AU - Bao L AD - Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Beijing, China; Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing, China. FAU - Wang, Li AU - Wang L AD - Department of Clinical Microbiology, Linzi District People's Hospital, Huangong Road, Zibo City, Shandong Province, China; Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Huangong Road, Zibo City, Shandong Province, China; Linzi District People's Hospital Affiliated to Binzhou Medical University, Huangong Road, Zibo City, Shandong Province, China. FAU - Li, Fengdi AU - Li F AD - Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Beijing, China; Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing, China. FAU - Wen, Mingjie AU - Wen M AD - Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. FAU - Li, Hui AU - Li H AD - Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center of Respiratory Diseases, Beijing, China; Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. FAU - Deng, Wei AU - Deng W AD - Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Beijing, China; Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing, China. FAU - Zhang, Xulong AU - Zhang X AD - Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. FAU - Cao, Bin AU - Cao B AD - Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center of Respiratory Diseases, Beijing, China; Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. Electronic address: caobin_ben@163.com. LA - eng PT - Journal Article DEP - 20191112 PL - England TA - J Microbiol Immunol Infect JT - Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi JID - 100956211 RN - 0 (Antiviral Agents) RN - 0 (Cytokines) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Acute Lung Injury/*drug therapy/*prevention & control MH - Animals MH - Antiviral Agents/*therapeutic use MH - Cytokines/analysis/immunology MH - Disease Models, Animal MH - Female MH - Influenza A Virus, H1N1 Subtype/*drug effects/pathogenicity MH - Interferon-gamma/*antagonists & inhibitors MH - Lung/pathology/*virology MH - Mice MH - Mice, Inbred BALB C MH - Orthomyxoviridae Infections/*drug therapy/virology OTO - NOTNLM OT - H1N1 OT - IFN-gamma OT - Lung injury COIS- Declaration of Competing Interest There is no conflict of interest. EDAT- 2019/11/30 06:00 MHDA- 2021/10/30 06:00 CRDT- 2019/11/30 06:00 PHST- 2018/10/23 00:00 [received] PHST- 2019/06/10 00:00 [revised] PHST- 2019/07/19 00:00 [accepted] PHST- 2019/11/30 06:00 [pubmed] PHST- 2021/10/30 06:00 [medline] PHST- 2019/11/30 06:00 [entrez] AID - S1684-1182(18)30438-9 [pii] AID - 10.1016/j.jmii.2019.07.009 [doi] PST - ppublish SO - J Microbiol Immunol Infect. 2021 Jun;54(3):396-403. doi: 10.1016/j.jmii.2019.07.009. Epub 2019 Nov 12.